title: Krimpsiekte, associated with thalamic lesions, induced by the neurotoxic cardiac glycoside, cotyledoside, isolated from Tylecodon wallichii (Harv.) Toelken subsp. wallichii.
abstract: The specific neurotoxic principle of Tylecodon wallichii (Harv.) Toelken subsp. wallichii, the cause of krimpsiekte in small stock, was isolated and identified as the previously described cumulative bufadienolide, cotyledoside. Krimpsiekte was experimentally induced in two sheep by the repeated intravenous administration of cotyledoside at the rate of 0.01-0.015 mg/kg body mass. On day 9, both animals developed clinical signs typical of krimpsiekte, which is characterized by tremors, paresis and recumbency. Both sheep had difficulty in controlling their hindquarters when attempting to lie down. No significant electrocardiograph abnormalities were detected during the experiment which confirms that cotyledoside at low doses does not overtly affect the electrical activity of the heart. No gross lesions were observed in the sheep. The most significant microscopic lesions comprised mild brain oedema and pronounced vacuolation of the white matter of thalamic nuclei. These lesions might explain some of the motor function deficiencies clinically observed in this syndrome. The previously held contention that these neurotoxic cardiac glycosides are indeed the cause of krimpsiekte is, therefore, confirmed.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, South Africa.
authors.forename: C J
authors.initials: CJ
authors.lastname: Botha
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Lugt
authors.forename: G L
authors.initials: GL
authors.lastname: Erasmus
authors.forename: T S
authors.initials: TS
authors.lastname: Kellerman
authors.forename: R A
authors.initials: RA
authors.lastname: Schultz
authors.forename: R
authors.initials: R
authors.lastname: Vleggaar
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D002018:Bufanolides / Q000008:administration & dosage / Q000302:isolation & purification* / Q000506:poisoning; D002301:Cardiac Glycosides / Q000008:administration & dosage / Q000302:isolation & purification* / Q000506:poisoning; D004562:Electrocardiography; D005260:Female; D008297:Male; D009206:Myocardium / Q000473:pathology; D010939:Plant Poisoning / Q000473:pathology / Q000662:veterinary*; D010947:Plants, Toxic / Q000737:chemistry; D012756:Sheep; D012757:Sheep Diseases / Q000139:chemically induced / Q000473:pathology*
chemical_list: D002018:Bufanolides; D002301:Cardiac Glycosides; C038322:cotyledoside